title: Long term results of a phase 2 study of vincristine sulfate liposome injection (Marqibo(®) ) substituted for non-liposomal vincristine in cyclophosphamide, doxorubicin, vincristine, prednisone with or without rituximab for patients with untreated aggressive non-Hodgkin lymphomas.
abstract: Vincristine sulfate liposome injection (VSLI; Marqibo(®) ; M) is active in relapsed and refractory lymphomas, and approved in the United States for relapsed and refractory adult acute lymphocytic leukaemia. We evaluated VSLI (2·0 mg/m(2) without dose cap) substituted for non-liposomal vincristine (VCR) in a cyclophosphamide, doxorubicin, vincristine, prednisone ± ritiximab (CHOP±R) regimen, creating CHMP±R in 72 untreated, aggressive non-Hodgkin lymphoma patients, including 60 with diffuse large B-cell lymphoma (DLBCL). The overall response rate was 96% (69/72) including complete response (CR) in 65 (90%) and unconfirmed CR in 2 (3%). Median progression-free survival (PFS) and overall survival (OS) were not reached at median follow-up of 8 and 10·2 years, respectively. The 5- and 10-year PFS and OS were 75%, 63%, 87%, and 77%, respectively. Despite VSLI exposure of up to 35 mg, the safety profile of CHMP±R was comparable to that reported for CHOP±R. Grade 3 peripheral neuropathy was reported in 2 (3%) patients; there was no reported Grade 3/4 constipation. CHMP±R was highly active, generally well tolerated, and compared favourably to historical trials with R-CHOP in DLBCL. This enhanced activity probably reflects VCR dose intensification, pharmacokinetic optimization, and enhanced delivery afforded by VSLI. A Phase 3 trial of R-CHMP versus R-CHOP in elderly patients with untreated DLBCL is ongoing.
authors.affiliation: University of Texas M. D. Anderson Cancer Center (UTMDACC), Houston, TX 77030, USA. fhagemei@mdanderson.org
authors.forename: Fredrick
authors.initials: F
authors.lastname: Hagemeister
authors.forename: Maria Alma
authors.initials: MA
authors.lastname: Rodriguez
authors.forename: Steven R
authors.initials: SR
authors.lastname: Deitcher
authors.forename: Anas
authors.initials: A
authors.lastname: Younes
authors.forename: Luis
authors.initials: L
authors.lastname: Fayad
authors.forename: Andre
authors.initials: A
authors.lastname: Goy
authors.forename: Nam H
authors.initials: NH
authors.lastname: Dang
authors.forename: Arthur
authors.initials: A
authors.lastname: Forman
authors.forename: Peter
authors.initials: P
authors.lastname: McLaughlin
authors.forename: Leonard Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.forename: Barbara
authors.initials: B
authors.lastname: Pro
authors.forename: Jorge
authors.initials: J
authors.lastname: Romaguera
authors.forename: Felipe
authors.initials: F
authors.lastname: Samaniego
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Silverman
authors.forename: Andreas
authors.initials: A
authors.lastname: Sarris
authors.forename: Fernando
authors.initials: F
authors.lastname: Cabanillas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008081:Liposomes; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000009:adverse effects / Q000627:therapeutic use; D011379:Prognosis; D000069283:Rituximab; D016019:Survival Analysis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D008081:Liposomes; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011239:Prednisolone
keywords: dose intensification; liposome; lymphoma; sphingomyelin; vincristine